Cross—reactivity of antibodies against microbial proteins to human tissues as basis of Crohn’s disease and other autoimmune diseases

Abstract

AbstractBackgroundAutoimmune disease is generally a systemic inflammatory response with production of autoantibodies. In this study, we investigated the anti-microbial antibodies in circulation in cases of Crohn’s disease (CD), Sjogren’s syndrome (SS) and other autoimmune disease and their roles in the pathogenesis of these autoimmune diseases.Material and methodsWestern blot was used to determine the reactivity of human plasmas from patients with CD and SS as the primary antibodies against the whole microbial extracts. The microbial proteins reactive to patients’ plasma were further identified and the modified sandwich ELISA assays were used to determine the blood levels of antibodies against these microbial proteins in patients with CD and SS. Antibodies against the microbial proteins are used for immunohistochemical staining of normal human tissue.ResultsA group of 7 microbial proteins was identified reactive to the plasmas of patients with CD and SS including DNA-directed RNA polymerase B (RPOB), and elongation factor G (EF-G) fromStaphylococcus aureusandStaphylococcus pseudintermedius(S. aureusandS. pseudintermedius), ATP synthase alpha (ATP5a) and heat shock protein 65 (Hsp65) fromMycobacterium avium subspecies paratuberculosis(MAP), elongation factor Tu (EF-Tu) and outer membrane porin C (ompC) fromEscherichia Coli(E. coli). Anti-microbial antibodies can cross-react to normal human tissues. The levels of antibodies against the microbial proteins are significantly elevated in the patients with CD and SS.ConclusionThe levels of antibodies against the microbial proteins are significantly elevated in CD and SS. The cross-reactivity of the anti-microbial antibodies to human tissue provides a new mechanism of pathogenesis of autoimmune diseases such as CD and SS.